An integrated long range plan is outlined to investigate the ultrastructure and function of the lymphatic system and determine its role in insuring a continual movement of proteins and cells throughout the extracellular fluid phase. This movement is unidirectional from the blood stream to tissue fluids and then into lymphatics and again back to the blood stream. We will investigate the ultrastructural and physiological significance of lymphatics in the removal of fluids and cells from the serous cavities (peritoneal, pleural, and pericardial), and examine the surface of the diaphragm in order to characterize the types of cells which adhere and migrate on the mesothelial surface enroute to the submesothelial lymphatics of the diaphragm. We will apply labeling techniques in studies designed to localize foci within the serous cavities which give rise to exudate fluids rich in proteins and the site or sites of orgin for free cells in the serous cavities. The number of free cells in the serous cavities is markedly increased following the injection of irritants into the serous cavities which produce an inflammatory response. The structural and pathophysiological events which accompany this inflammatory process will be monitored to particularly determine the course of free cells within the peritoneal cavity which include their entrance, migration, adhesion, and subsequent removal from the peritoneal cavity by the lymphatics. We will also determine the distribution of lectin-binding sites on the surfaces of lymph node cells and characterize those changes which occur following antigen stimulation. To accomplish these objectives, the combined methods and techniques of histology, cytochemistry, biochemistry, immunocytochemistry, transmission and scanning electron microscopy, backscattered electron imaging, and freeze-fracture replication will be brought to bear on the projects outlined in this research proposal.